The use of probiotics appears to lower the risk of developing diarrhea while taking antibiotic therapy, based on a systematic review of 82 randomized clinical trials in the May 9 issue of JAMA.
The majority of the studies, however, were poorly conducted with considerable limitations, and more research is needed to determine which probiotics are associated with the greatest efficacy in the setting of specific antibiotics, said Susanne Hempel, Ph.D., of the Southern California Evidence-Based Practice Center, Rand Health, Santa Monica, and her associates.
In fact, when examined individually, most of the studies showed no significant benefit from using probiotics. However, when the results of 63 of these trials were pooled in a meta-analysis involving 11,811 subjects, the use of probiotics decreased the relative risk of developing antibiotic-related diarrhea when compared with not using them, the investigators found.
Adjunct probiotic therapy also reduced the number of study subjects who experienced severe diarrhea, they added.
The investigators reviewed the literature in 12 electronic databases and screened 2,426 reports on probiotic use published during the last 30 years. They included 82 randomized clinical trials that compared the therapy against no treatment, placebo, or a different dose of probiotics in their meta-analysis.
The study subjects included children, adults, and the elderly who were taking antibiotics for a variety of indications. Sixteen of the trials examined the use of a single antibiotic, and the remainder assessed numerous antibiotics. Two trials focused on the use of probiotics to treat rather than to prevent antibiotic-associated diarrhea.
All types of probiotics were included in the meta-analysis, including the genera Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, and Bacillus, alone or in various combinations.
Overall, the quality of the research was considered low. Fifty-nine studies "lacked adequate information to assess the overall risk of bias." Sixty-four never stated whether treatment allocation was blinded, 31 didn’t report an intent-to-treat analysis, and approximately half did not include a calculation of the study’s statistical power to detect differences in outcomes.
In addition, 17 trials were industry sponsored, and 52 did not clarify the role of funding or conflicts of interest. Perhaps most important, 59 of the 82 randomized clinical trials did not report on adverse events specifically related to the use of probiotics, Dr. Hempel and her colleagues said.
Probiotics have been linked to serious adverse effects such as fungemia and bacterial sepsis. "It is noteworthy that few trials addressed these outcomes, especially because cases of such infections suspected to be associated with the administered organisms were reported decades ago," Dr. Hempel and her associates noted.
The use of probiotics was found to reduce the risk of antibiotic-associated diarrhea, with a relative risk of 0.58. This benefit was consistent across several subgroups of patients and in different sensitivity analyses.
"The treatment effect equates to a number needed to treat of 13," the investigators said (JAMA 2012;307:1959-69).
There was no evidence that the benefit varied by type of probiotic, but it was impossible to assess this question adequately because most of the trials used blends of genera, species, and strains.
The treatment benefit appeared to be consistent regardless of patient age, the clinical indication for antibiotic therapy, and the duration of antibiotic therapy. It wasn’t possible to assess the advantages of probiotics by type of antibiotic agent because the trials in this meta-analysis rarely specified which antibiotics were used, or else they involved patients taking a variety of antibiotics.
This study was funded by Rand. No relevant financial relationships were reported.